Nonionic Amphiphilic Copolymers of Poly(poly(ethylene Glycol) Methacrylate) Brushes with Methyl Methacrylate Prepared by Atom Transfer Radical Polymerization as Dry Solid Polymer Electrolytes for Next Generation Li-ion Battery Applications.

Amphiphilic copolymers of comb-like poly(poly(ethylene glycol) methacrylate) (PPEGMA) with methyl methacrylate (MMA) synthesized by one-pot atom transfer radical polymerization were mixed with lithium bis (trifluoromethanesulfonyl) imide salt to formulate dry solid polymer electrolytes (DSPE) for semisolid-state Li-ion battery applications. The PEO-type side chain length (EO monomer's number) in the PEGMA macromonomer units was varied, and its influence on the mechanical and electrochemical characteristics was investigated. It was found that the copolymers, due to the presence of PMMA segments, possess viscoelastic behavior and less change in mechanical properties than a PEO homopolymer with 100 kDa molecular weight in the investigated temperature range.

A generic approach based on long-lifetime fluorophores for the assessment of protein binding to polymer nanoparticles by fluorescence anisotropy.

Quantitation of protein-nanoparticle interactions is essential for the investigation of the protein corona around NPs and when using synthetic polymer nanoparticles as affinity reagents for selective protein recognition . Here, a method based on steady-state fluorescence anisotropy measurement is presented as a novel, separation-free tool for the assessment of protein-nanoparticle interactions. For this purpose, a long-lifetime luminescent Ru-complex is used for protein labelling, which exhibits low anisotropy when conjugated to the protein but displays high anisotropy when the proteins are bound to the much larger polymer nanoparticles.

The interaction between mucin and poly(amino acid)s with controlled cationic group content in bulk phase and in thin layers.

The type and concentration of charged groups in polymers have a key role in mucoadhesive interactions. A series of cationic poly(amino acid)s with different charge densities was designed to unravel the correlation between chemical structure and mucin-polymer interactions. Colloidal interactions between the mucin protein and synthetic polyaspartamides were tested by dynamic light scattering, zeta potential measurements and turbidimetric titration as a function of polymer-to-mucin mass ratio.

In situ gelation of thiolated poly(aspartic acid) derivatives through oxidant-free disulfide formation for ophthalmic drug delivery.

Efficient topical treatment of ocular diseases requires a prolonged residence time of drug formulations. An in situ gelling, mucoadhesive system can provide improved residence time while keeps the installation of the formulation easy and accurate due to its low initial viscosity. We synthesized a two-component, biocompatible water-based liquid formulation showing in situ gelation upon mixing.

Cyclodextrin-enabled nepafenac eye drops with improved absorption open a new therapeutic window.

Nepafenac is a highly effective NSAID used for treating postoperative ocular inflammation and pain after cataract surgery and its advantage over conventional topical NSAIDs has been proved many times. However, Nevanac® is a suspension eye drop, which clearly lacks patient compliance causing irritation, blurred vision, foreign body sensation along with problematic dosage due to its sticky, inhomogeneous consistence. In this study, nepafenac containing eye drops were prepared using hydroxypropyl-β-cyclodextrin to ensure complete dissolution of nepafenac, sodium hyaluronate to provide mucoadhesion and adequate viscosity and a preservative-free officinal formula, Oculogutta Carbomerae containing carbomer (just like Nevanac®), therefore providing a similar base for the new formulations.

Poly(dithiophosphate)s, a New Class of Phosphorus- and Sulfur-Containing Functional Polymers by a Catalyst-Free Facile Reaction between Diols and Phosphorus Pentasulfide.

Novel poly(dithiophosphate)s (PDTPs) were successfully synthesized under mild conditions without any additive in the presence of THF or toluene diluents at 60 °C by a direct, catalyst-free reaction between the abundant phosphorus pentasulfide (PS) and glycols such as ethylene glycol (EG), 1,6-hexanediol (HD) and poly(ethylene glycol) (PEG). GPC, FTIR, H and P NMR analyses proved the formation of macromolecules with dithiophosphate coupling groups having P=S and P-SH pendant functionalities. Surprisingly, the ring-opening of THF by the P-SH group and its pendant incorporation as a branching point occur during polymerization.

Thiolated cationic poly(aspartamides) with side group dependent gelation properties for the delivery of anionic polyelectrolytes.

gellable polymers have potential applications as injectable formulations in drug delivery and regenerative medicine. Herein, thiolated cationic polyaspartamides were synthesised two different approaches to correlate the side group structure with gelation properties, gel strength and drug release kinetics. Cysteamine (CEA) was used as a thiolating agent to prepare thiolated cationic polyaspartamide groups with short thiolated side groups.

Synthesis, complex formation and corneal permeation of cyclodextrin-modified, thiolated poly(aspartic acid) as self-gelling formulation of dexamethasone.

The present study aimed at developing a potential in situ gellable dexamethasone (DXM) eye drop. Poly(aspartic acid) (PASP) derivatives were synthesized with dual functionality to improve the solubility of DXM, and to achieve in situ gelation. First, amine-modified β-cyclodextrin (CD) was attached to polysuccinimide (PSI), second, thiol functionalities were added by the reaction of cysteamine and succinimide rings.

Long-Term Aging of Concentrated Aqueous Graphene Oxide Suspensions Seen by Rheology and Raman Spectroscopy.

Today, graphene oxide (GO) has gained well-deserved recognition, with its applications continuing to increase. Much of the processing of GO-based devices occurs in a dispersed form, which explains the commercialization of GO suspensions. Aging of these suspensions can, however, affect the shelf life and thus their application potential.

A robust mucin-containing poly(vinyl alcohol) hydrogel model for the in vitro characterization of mucoadhesion of solid dosage forms.

Mucoadhesion testing at macroscopic scale needs a robust, convenient in vitro method as ex vivo methods suffer from poor reproducibility and ethical problems. Here we synthesized mucin-free poly(vinyl alcohol) (PVA) and mucin-containing PVA hydrogel substrates (Muc/PVA) to measure adhesion of polymer tablets. Freezing-thawing method was used for gelation to avoid chemical cross-linking and to preserve the functionality of mucin.

Nanofibrous Formulation of Cyclodextrin Stabilized Lipases for Efficient Pancreatin Replacement Therapies.

Enzyme replacement therapies (ERT) have been of great help over the past 30 years in the treatment of various lysosomal storage disorders, including chronic pancreatitis and its common complication, exocrine pancreatic insufficiency. Research shows that difficulties in designing such drugs can be overcome by using appropriate additives and various enzyme immobilization techniques. Cyclodextrins (CDs) can be considered as a promising additive for enzyme replacement therapies, as they are known to enhance the activity of enzymes in a complex process due to their specific binding.

Magnetic Nanoparticles with Dual Surface Functions-Efficient Carriers for Metalloporphyrin-Catalyzed Drug Metabolite Synthesis in Batch and Continuous-Flow Reactors.

The dual functionalization of magnetic nanoparticles with inert (methyl) and reactive (aminopropyl) groups enables efficient immobilization of synthetic metalloporphyrins (such as 5,10,15,20-tetrakis(2,3,4,5,6-pentafluorophenyl)iron(II) porphyrin and 5,10,15,20-tetrakis-(4-sulfonatophenyl)iron(II) porphyrin) via covalent or ionic interactions. The proportion of reactive function on the surface has significant effect on the biomimetic activity of metalloporphyrins. The optimized magnetic nanocatalyst containing porphyrin was successfully applied for biomimetic oxidation of antihypertensive drug Amlodipine in batch and continuous-flow reactors as well.

Binding Modes of a Phenylpyridinium Styryl Fluorescent Dye with Cucurbiturils.

In order to explore how cucurbituril hosts accommodate an -phenyl-pyridinium derivative guest, the complexation of the solvatochromic dye, 4-(4-(dimethylamino)styryl)-1-phenylpyridinium iodide (PhSt) with -tetramethyl-cucurbit[6]uril (MeCB6) and cucurbit[7]uril (CB7) was investigated by absorption spectroscopic, fluorescence and NMR experiments. In aqueous solutions, PhSt forms 1:1 complexes with both cucurbiturils, the complex with CB7 has a higher stability constant ( = 6.0 × 10 M) than the complex with MeCB6 ( = 1.

Ecotoxicity Assessment of Graphene Oxide by through a Multimarker Approach from the Molecular to the Physiological Level including Behavioral Changes.

The extensive use of engineered nanomaterials, such as graphene oxide (GO), is stimulating research about its potential environmental impacts on the aquatic ecosystem. This study is aimed to comprehensively assess the acute toxicity of a well-characterized GO suspension to . Conventional ecotoxicological endpoints (lethality, immobilization) and more sensitive, sublethal endpoints (heartbeat rate, feeding activity, and reactive oxygen species (ROS)) production were used.

Mucoadhesive interactions between synthetic polyaspartamides and porcine gastric mucin on the colloid size scale.

Synthetic polyaspartamides with various functional side groups including primary, secondary, tertiary amine or carboxyl groups were designed to explore the effect of chemical composition on polymer-mucin interactions. Since the molecular weight of the polymers and the degree of modification were identical for each derivative, the role of the functional groups could be evaluated. Chitosan was used as a control sample due to its strong interaction with mucin primarily through electrostatic forces.

Liver-on-a-Chip‒Magnetic Nanoparticle Bound Synthetic Metalloporphyrin-Catalyzed Biomimetic Oxidation of a Drug in a Magnechip Reactor.

Biomimetic oxidation of drugs catalyzed by metalloporphyrins can be a novel and promising way for the effective and sustainable synthesis of drug metabolites. The immobilization of 5,10,15,20-tetrakis(2,3,4,5,6-pentafluorophenyl)iron(II) porphyrin (FeTPFP) and 5,10,15,20-tetrakis-(4-sulfonatophenyl)iron(II) porphyrin (FeTSPP) via stable covalent or rapid ionic binding on aminopropyl-functionalized magnetic nanoparticles (MNPs-NH) were developed. These immobilized catalysts could be efficiently applied for the synthesis of new pharmaceutically active derivatives and liver related phase I oxidative major metabolite of an antiarrhythmic drug, amiodarone integrated in a continuous-flow magnetic chip reactor (Magnechip).

Mucoadhesive Cyclodextrin-Modified Thiolated Poly(aspartic acid) as a Potential Ophthalmic Drug Delivery System.

Thiolated poly(aspartic acid) is known as a good mucoadhesive polymer in aqueous ophthalmic formulations. In this paper, cyclodextrin-modified thiolated poly(aspartic acid) was synthesized for the incorporation of prednisolone, a lipophilic ophthalmic drug, in an aqueous in situ gellable mucoadhesive solution. This polymer combines the advantages of cyclodextrins and thiolated polymers.

The effect of the antioxidant on the properties of thiolated poly(aspartic acid) polymers in aqueous ocular formulations.

Thiolated polymers are a promising new group of excipients, but their stability against atmospheric oxidation has not been investigated in detail, and only a few efforts have been made to improve their stability. The oxidation of the thiol groups in solutions of thiolated polymers may result in a decrease of mucoadhesion and unpredictable in situ gelation. The aims of our work were to study the stability of aqueous solutions of thiolated polymers and the effects of stabilizing agents.

Structure-biocompatibility and transfection activity relationships of cationic polyaspartamides with (dialkylamino)alkyl and alkyl or hydroxyalkyl side groups.

A series of 14 cationic derivatives of poly(aspartic acid) i.e. cationic polyaspartamides with different (dialkylamino)alkyl and alkyl or hydroxyalkyl side groups was synthesized by nucleophilic addition on polysuccinimide.

Poly(aspartic acid) with adjustable pH-dependent solubility.

Unlabelled: Poly(aspartic acid) (PASP) derivatives with adjustable pH-dependent solubility were synthesized and characterized to establish the relationship between their structure and solubility in order to predict their applicability as a basic material for enteric coatings. Polysuccinimide, the precursor of PASP, was modified with short chain alkylamines, and the residual succinimide rings were subsequently opened to prepare the corresponding PASP derivatives. Study of the effect of the type and concentration of the side groups on the pH-dependent solubility of PASP showed that solubility can be adjusted by proper selection of the chemical structure.

Cationic Thiolated Poly(aspartamide) Polymer as a Potential Excipient for Artificial Tear Formulations.

Dry eye disease is a relatively common ocular problem, which causes eye discomfort and visual disorders leading to a decrease in the quality of life. The aim of this study was to find a possible excipient for eye drop formulations, which is able to stabilize the tear film. A cationic thiolated polyaspartamide polymer, poly[(N-mercaptoethylaspartamide)-co-(N-(N',N'-dimethylaminoethyl)aspartamide)] (ThioPASP-DME), was used as a potential vehicle.

In vitro testing of thiolated poly(aspartic acid) from ophthalmic formulation aspects.

Ocular drug delivery formulations must meet anatomical, biopharmaceutical, patient-driven and regulatory requirements. Mucoadhesive polymers can serve as a better alternative to currently available ophthalmic formulations by providing improved bioavailability. If all requirements are addressed, a polymeric formulation resembling the tear film of the eye might be the best solution.

Supermacroporous chemically cross-linked poly(aspartic acid) hydrogels.

Chemically cross-linked poly(aspartic acid) (PASP) gels were prepared by a solid-liquid phase separation technique, cryogelation, to achieve a supermacroporous interconnected pore structure. The precursor polymer of PASP, polysuccinimide (PSI) was cross-linked below the freezing point of the solvent and the forming crystals acted as templates for the pores. Dimethyl sulfoxide was chosen as solvent instead of the more commonly used water.

[Use of a novel polymer, the in-situ gelling mucoadhesive thiolated poly(aspartic acid) in ophthalmic drug delivery].

The bioavailability of drugs used on mucosal surfaces can be increased by the use of mucoadhesive polymers. A new type of mucoadhesive polymers is the group of thiolated polymers with thiol group containing side chains. These polymers are able to form covalent bonds (disulphide linkages) with the mucin glycoproteins.

Thiolated poly(aspartic acid) as potential in situ gelling, ocular mucoadhesive drug delivery system.

The ophthalmic formulations on the market suffer from poor bioavailability, and it would therefore be useful to design a new formulation which is able to prolong the residence time and reduce the administration frequency. Polymer matrices which exhibit strong mucoadhesion are promising platforms in ocular drug delivery from the aspect of improved bioavailability. In the present study, an in situ gelling, mucoadhesive drug delivery system was fabricated from thiolated poly(aspartic acid) (ThioPASP).